Term
|
Definition
| 1. Water insoluble biological compound soluble in fat solvents |
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|
Term
| 2. What properties define whether a substance is called a lipid or not? |
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Definition
|
|
Term
| 3. Give some examples of lipids |
|
Definition
| 3. Fatty acids, TAG, TG, cholesterol, membrane phospholipids, steroid hormones, etc. |
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Term
| 4. Describe the structure of a fatty acid |
|
Definition
| 4. Long chain carboxylic acid |
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|
Term
| 5. What is the name for a 16C saturated FA? |
|
Definition
| 5. Palmitic acid (ionized form = palmitate) |
|
|
Term
| 6. From which end does the numbering system using ω start? α? |
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Definition
| 6. Hydrocarbon end; Acid end |
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|
Term
| 7. What is a 18C monounsaturated FA? |
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Definition
|
|
Term
| 8. What is the major dietary lipid? |
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Definition
|
|
Term
| 9. What composes bile salts? |
|
Definition
| 9. Cholesterol esters (planar ring structure with hydroxyl groups facing towards hydrophilic surface, and steroidal surface facing hydrophobic areas) |
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|
Term
| 10. What digests TG into monoacylglycerols and diacylglycerols? |
|
Definition
| 10. Lipase (gastric or pancreatic) |
|
|
Term
| 11. What protein binds to lipase and stabilizes it by displacing a bile salt in a micelle? |
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Definition
|
|
Term
| 12. What enzyme cleaves cholesterol esters? |
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Definition
|
|
Term
| 13. What enzyme cleaves FA from TAG at the 2 position? |
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Definition
|
|
Term
| 14. Through what circulation are bile salts returned to the liver? |
|
Definition
| 14. enterohepatic circulation |
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Term
| 15. How much (percentage) of the bile salt pool is excreted? |
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Definition
|
|
Term
| 16. How is a FA activated? |
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Definition
| 16. Acylated by addition of CoAsh (high energy thioester) utilizing ATP to AMP, produces FA-CoA |
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|
Term
| 17. How many high energy phosphate bonds are required for FA activation in their oxidative catabolism? |
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Definition
|
|
Term
| 18. What carries FA into the lymphatic system? |
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Definition
|
|
Term
| 19. What composes most of a chylomicron? |
|
Definition
|
|
Term
| 20. Are cholesterols present in chylomicrons? |
|
Definition
| 20. Yes (hydroxyl groups pointed out) |
|
|
Term
| 21. If the B –apoprotein gene is going to produce a protein destined for the liver how much of the AA transcript is transcribed? |
|
Definition
| 21. 100%, thus its termed ApoB-100 |
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|
Term
| 22. If the B –apoprotein gene is going to produce a protein destined for the intestine how much of the AA transcript is transcribed? |
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Definition
|
|
Term
| 23. What transfers proteins to ApoB particles? |
|
Definition
| 23. Micosomal TG transfer protein (MTP) |
|
|
Term
| 24. What organelle is responsible for apo particle maturation and secetion? |
|
Definition
|
|
Term
| 25. Where are chylomicrons synthesized? |
|
Definition
| 25. Intestinal epithelial cell |
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|
Term
| 26. Where is a TG converted to 2-MG or FA ? (free fatty acids) |
|
Definition
|
|
Term
| 27. Where is the TG resynthesized? |
|
Definition
| 27. Intestinal epithelial cell |
|
|
Term
| 28. Where are nascent chylomicons? |
|
Definition
|
|
Term
| 29. What forms a mature chylomicron? |
|
Definition
| 29. ApoCII added by HDL+ApoE |
|
|
Term
| 30. What activates mature CM? |
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Definition
|
|
Term
| 31. Where does the released FA travel to? |
|
Definition
| 31. Muscles, adipose tissue, etc. |
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|
Term
| 32. Where does the glycerol travel to? |
|
Definition
| 32. Liver (glycerol cycle) |
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|
Term
| 33. Does the same glycerol cleaved take part in TAG resynthesis for instance in adipocytes? |
|
Definition
| 33. No, it’s a new glycerol molecule |
|
|
Term
| 34. Are fatty acids a source of energy for all tissues? |
|
Definition
|
|
Term
| 35. How much energy does oxidation of fat yield? |
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Definition
|
|
Term
| 36. What are fats largely ingested as? |
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Definition
|
|
Term
| 37. What pathway oxidizes FA? |
|
Definition
|
|
Term
| 38. How are FA transported? |
|
Definition
| 38. bound to serum albumin |
|
|
Term
| 39. What are some examples of saturated fA? |
|
Definition
| 39. palmitate (16C), stearate (18C), arachidate (20C) |
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|
Term
| 40. What are some examples of monounsaturated FA? |
|
Definition
| 40. palmitoleate, oleate (18C) |
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|
Term
| 41. What are some examples of polyunsaturated FA (PUFA)? |
|
Definition
| 41. linoleic, linolenic, arachidonic |
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|
Term
| 42. What bond is cleaved in beta-oxidation? |
|
Definition
| 42. α-β bond (by standard organic chemistry nomenclature convention) |
|
|
Term
| 43. What FA can humans not synthesize, thus require in diet? |
|
Definition
|
|
Term
| 44. Does glucagon stimulate FA synthesis? |
|
Definition
| 44. no, it stimulates lipolysis |
|
|
Term
| 45. Describe hepatic glycerol metabolism. |
|
Definition
| 45. Gycerol kinase phosphorylates glycerol to glycerol 3 phosphateàG3P DHàGNG |
|
|
Term
| 46. What two hormones increase cAMP levels and in turn lipolysis (via PKA actions on Hormone sensitive lipase)? |
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Definition
|
|
Term
| 47. What is an antilipolytic hormone? |
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Definition
|
|
Term
| 48. What can lack of insulin in Type 1 diabetes lead to ( in terms of FA metabolism)? |
|
Definition
|
|
Term
| 49. What are long chain FA’s carried on in the blood? |
|
Definition
|
|
Term
| 50. How is a FA transported across the mitochondrial membrane? |
|
Definition
| 50. Transport coupled to carnitine (which is mt. membrane soluble) |
|
|
Term
| 51. What happens to FA in the mitochondria? |
|
Definition
| 51. Oxidizing environment, NAD is high relative to NADHà rx. Favoring reducing equivalents favored and NADH/FADH2 produced for energy utilization via CAC,ETC, KB,etc. |
|
|
Term
| 52. How are FA’s activated in order to form FA-CoA |
|
Definition
| 52. FA-CoA synthetase claves ATP to AMP (2 high energy bonds) to produce FA-CoA and pyrophosphate (uses the energy from repulsion,entropy,resonance of ATP to form a high energy thioester bond, energy is conserve) |
|
|
Term
| 53. How many high energy phosphate bonds are required just for activation of FA to FA-CoA? |
|
Definition
|
|
Term
| 54. What nucleotide is cleaved to activate FA? |
|
Definition
| 54. ATP to AMP.. if you miss this now you deserve to get it wrong |
|
|
Term
| 55. What is the method of transport for short and medium chain FA’s into the mt.? |
|
Definition
|
|
Term
| 56. What is the method of transport for long chain FA’s into the mt.? |
|
Definition
|
|
Term
| 57. Where are very long chain FA’s oxidized? |
|
Definition
|
|
Term
| 58. What are the enzymes that reversibly transport FA-CoA and Fa-Carnitine in the mt.? |
|
Definition
| 58. Carnitine-palmitoyl-transferase 1 and 2 (CPT1,CPT2); CPT1 is on outer mt membrane, CPT2 is on inner membrane (reforms FA-CoA and releases carnitine inside mt.) |
|
|
Term
| 59. Is there a shuttle for FA-CoA? |
|
Definition
| 59. If there was, why are we talking about all this carnitine transport business |
|
|
Term
| 60. What is the first step of β-oxidation |
|
Definition
| 60. AcylCoA DH takes 2e- out into FADH2 from saturated FA, oxidizes alpha-beta carbon bond to alkene |
|
|
Term
| 61. What is the second step of β-oxidation |
|
Definition
| 61. Hydration via enoy CoA hydratase |
|
|
Term
| 62. Describe the action of glucagon on lipolysis |
|
Definition
| 62. Glucagon receptoràGsàACàcAMP via ATPàPKAàhormone sensitive lipase and perilipins phosphorylatedàdegradation of TAG |
|
|
Term
| 63. What is the third step of β-oxidation? |
|
Definition
| 63. B-hydroxyacylCoA DH , oxidizes hydroxyl to ketone & produces NADH |
|
|
Term
| 64. What is the fourth step of β-oxidation? |
|
Definition
| 64. β-ketothiolase (cleaves terminal Acyl-CoA), reverse claisen condensation, thioester attached to ketone of beta carbon is good for nucleophilic attack |
|
|
Term
| 65. How many rounds of β-oxidation to completely breakdown oleate? |
|
Definition
|
|
Term
| 66. How many rounds of β-oxidation to completely breakdown palmitate? |
|
Definition
|
|
Term
| 67. What is similarity between CAC and β-oxidation? |
|
Definition
| 67. Hydration, and oxidation of metabolites to produce FADH2 and NADH |
|
|
Term
| 68. Where is AcylCoA synthetase located? |
|
Definition
| 68. Bound to outer mt. membrane |
|
|
Term
| 69. Why can short and medium chain FA enter mt but not long chains? |
|
Definition
| 69. …large ones are bigger à can’t diffuse..recall the pores acoss mt are membrane are selective for size |
|
|
Term
| 70. Why is the AcylCoA synthetase rx irreversible? |
|
Definition
| 70. Entropy, imagine trying to rearrange PPi to ATP with so very few PPi’s present (cleavage of PPi and the thioster bond is similar in free energy) |
|
|
Term
| 71. How does free carnitine return across the membrane? |
|
Definition
|
|
Term
|
Definition
| 72. malonyl coA a FA synthesis precursor |
|
|
Term
| 73. What is the logic of CPT1/2? |
|
Definition
| 73. FA’s are carried via O-acyl carnitine linkages which have an eq. constant near 1, due to orbital overlap bw C and O , usually this is not the case however it takes the place of the high energy due to thioeser bonds that have less overlap beteen S and C therefore less resonance stabilization and less energy than usual |
|
|
Term
| 74. What is the regulated step of FA oxidation? |
|
Definition
| 74. CPT1, entry into mt. recall cytosol and mt have diff. CoA pools (mt is used for ox, cyt. Is used for synthesisàcompartmentalization once we move between pools we are more or less committed to the pathway). |
|
|
Term
| 75. How are electrons transferred from FADH to ETC? |
|
Definition
| 75. ETFàCoQàETC via a series of semiquinones,etc. |
|
|
Term
| 76. How many ATP’s are generated by oxidation of a saturated 16 C FA? |
|
Definition
| 76. 7 FADH2 x 1.5, 7 NADH x 2.5, 8 AcetylCoA x 10, - 2 ATP = 106 ATP |
|
|
Term
| 77. How many ATP’s are generated by oxidation of a saturated 22 C FA? |
|
Definition
|
|
Term
| 78. How many ATP’s are generated by oxidation of a saturated 49 C FA? |
|
Definition
|
|
Term
| 79. How many ATP’s are generated by oxidation of a saturated 109 C FA? |
|
Definition
| 79. 757, so how do I get these #? Use the formula 2(N-2)+5N-2 for any saturated FA where N = # of carbons |
|
|
Term
| 80. How many ATP’s are generated by oxidation of palmitate (d16:9)? |
|
Definition
| 80. 102 (loss of first round and usage of NADPH) |
|
|
Term
| 81. What is the major control of FA oxidation? |
|
Definition
|
|
Term
| 82. What enzyme does insulin stimulate in FA synthesis? |
|
Definition
| 82. ACC (Acetyl CoA carboxylase) |
|
|
Term
| 83. What is different in oxidation of unsaturated FA? |
|
Definition
| 83. Isomerizes from cis unconjugated double bonds via enoylCoA isomerae to trans, cisàcontinue beta oxàreduce conjugated double bond via 2,4 dienoyl CoA reductase (uses NADPH) and produces trans d3 and is then isomerized into trans d2 |
|
|
Term
| 84. What is different in oxidation of odd chain FA? |
|
Definition
| 84. Production of propionyl CoA upon terminal rx of beta ox àpropionyl CoA carboxylase (uses 1ATP for AMP) to produce methylmalony CoA via an epimeraseàmutase to produce succinyl CoA à run it through TCA for 1 GTP, 1 FADH2 and 1 NADH (basically lose 2NADH from AKG DH,isocitrate DH) |
|
|
Term
| 85. What vitamin does methylmalonyl coa mutase require? |
|
Definition
| 85. B12 (corrin ring structure) |
|
|
Term
| 86. What is the 1st step of peroxisome oxidation of FA? |
|
Definition
| 86. AcylCoa DH (makes FADH2 and peroxide) |
|
|
Term
| 87. What step is diff. in peroxisomal oxidation of FA? How many times is oxidation repeated? |
|
Definition
| 87. 1st step, until chain is 6-10C’s ong and can be transported to mt. where oxidation is completed |
|
|
Term
| 88. What type of oxidation is used in peroxisome? What disease is correlated with a defect in this? |
|
Definition
| 88. Alpha oxidation, Refsun’s disease |
|
|
Term
| 89. Where does omega-oxidation take place? |
|
Definition
|
|
Term
| 90. What is the most common sort of deficiencies in FA oxidation? |
|
Definition
| 90. Oxidation of MCAD’s: treatment is to avoid fasting, eat meals with less fat to control lipolysis and decrease dependence on ketones |
|
|
Term
| 91. What is the energy diff. in peroxisomal oxidation of FA? |
|
Definition
| 91. Loss of energy from first step (still produces FADH but is not coupled to ETC since its not in mt, transfers e- instead to peroxide) |
|
|
Term
| 92. What accounts for most of energy stores in vivo? |
|
Definition
|
|
Term
| 93. Second largest source? |
|
Definition
|
|
Term
| 94. Describe (Briefly lipolysis) |
|
Definition
| 94. TAGàFFAàAcylCoA & glycerol |
|
|
Term
| 95. Describe insulin/glucagon ratio in fed state. |
|
Definition
|
|
Term
| 96. In order to get G3P in fat cells we must start with what precursor? |
|
Definition
| 96. Glucose, Adipose doesn’t have GNG enzymes |
|
|
Term
| 97. What cycle recycles lactate/glucose from muscle/liver? |
|
Definition
|
|
Term
| 98. How is nitrogen waste utilized? |
|
Definition
|
|
Term
| 99. In the starved state what becomes a major souce of energy? |
|
Definition
| 99. Ketone bodies from FA oxidation |
|
|
Term
|
Definition
| 100. Acetoacetate, B-hydroxybutyrate |
|
|
Term
| 101. In KB synthesis what removes CoA to allow 2 AcetylCoA’s to be joined? |
|
Definition
|
|
Term
| 102. What enzyme forms HMG CoA? |
|
Definition
|
|
Term
| 103. How is acetoacetate formed from HMG CoA? |
|
Definition
|
|
Term
| 104. If cellular NADH is high what can acetoacetate become? |
|
Definition
| 104. Β-hydroxybutyrate via B-hydroxybutyrate DH using NADH |
|
|
Term
| 105. Acetoacetate can spontaneously decarboxylate to what ? |
|
Definition
|
|
Term
| 106. KB are only made where? |
|
Definition
|
|
Term
| 107. How can KB be broken down? |
|
Definition
| 107. Succinyl CoA acetoacetate CoA transferase adding CoA onto acetoacetate (acetoacetylCoA) which can be broken down into two acetyl CoA’s |
|
|
Term
| 108. What regulates ketone synthesis? |
|
Definition
| 108. Availability of FA (malonyl CoA inhibits CPT1) |
|
|
Term
| 109. What is the goal of FA synthesis? |
|
Definition
| 109. Store glucose breakdown products as FA |
|
|
Term
| 110. What are FA stored as? |
|
Definition
|
|
Term
| 111. How are hepatic TAG exported from liver? |
|
Definition
|
|
Term
| 112. What does the fatty aid synthase complex form? |
|
Definition
|
|
Term
| 113. Where does FA synthesis occur? |
|
Definition
|
|
Term
| 114. What does FA synthesis use to build FA chains primarily? |
|
Definition
| 114. Acetyl CoA, malonyl CoA, NADPH, FADH2, also requires pantotheic acid for FA synthase complex |
|
|
Term
| 115. What TCA intermediate can be shunted for FA synthesis? How is this done? |
|
Definition
| 115. Citrate by using citrate lyase to form Acetyl CoA |
|
|
Term
| 116. What reducing equivalent does FA synthase complex use for FA synthesis? |
|
Definition
|
|
Term
| 117. How do FA leave liver? How are they released? |
|
Definition
| 117. VLDL via lipoprotein lipase |
|
|
Term
| 118. What enzyme provides cytosolic NADPH for FA synthesis? There are two possible answers to this question. |
|
Definition
| 118. Malic enzyme (reduces malate), or PPP via G6P DH (oxidative portion) |
|
|
Term
| 119. What else can citrate provide for FA synthesis? |
|
Definition
| 119. AcetylCoA via citrate lyase (OAA becomes malate via malate DH) |
|
|
Term
| 120. Describe the citrate cycle |
|
Definition
| 120. Citrate Synthase (OAA+AcCoA)àCitrate lyase (now in cytosol, to reproduce OAA and AcCoA) using ATPàMalate DH makes malate from OAA àmalic enzyme produces NADPH or FA synthesisàpyruvate carboxylaseàback to OAA (logic is to keep NAD/NADP pools distinct in cell) |
|
|
Term
| 121. What is the substrate and products of the malic enzyme rx.? |
|
Definition
| 121. Malate; carbon dioxide, NADH, and pyruvate respectively |
|
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Term
| 122. What is the first committed step of FA synthesis? |
|
Definition
| 122. Acetyl Coa carboxylase (also uses biotin cofactor) takes carbon dioxide and adds to acetyl CoA to make malonyl CoA while cleaving ATP to ADP |
|
|
Term
| 123. T or F: Phosphorylated ACC is the active form |
|
Definition
| 123. F, ACC is pophorylated by AMP activated protein kinase (when energy is low)àstop synthesis b/c we need energy |
|
|
Term
| 124. What long term regulation is ACC under? |
|
Definition
| 124. Transcriptional regulation |
|
|
Term
| 125. T or F: in mammals all rx. By FA synthase are catalyzed by distinct separate enzymes? |
|
Definition
| 125. F: these enzymes are coupled in a multi enzymatic complex known as FA synthase |
|
|
Term
| 126. What portion of FA synthase attaches to FA synthesis intermediates? |
|
Definition
| 126. ACP portion has phopspho-pantetheinyl prosthetic group (two sulfhydryl groups) |
|
|
Term
| 127. FA synthase is a _____________ (tertiary structure) |
|
Definition
|
|
Term
| 128. What is ACP attached to? |
|
Definition
|
|
Term
| 129. What is the 1st step of FA synthase? |
|
Definition
| 129. Transfer of malonyl CoA to synthase (after FA synthase is primed with AcetylCoA on other sulfhydryl pantothenic acid group) |
|
|
Term
| 130. What is the 2nd step? |
|
Definition
| 130. Condensation of malonyl and acyl groups |
|
|
Term
| 131. What is the 3rd step? |
|
Definition
| 131. Reduction of b-ketoacyl group using NADPH |
|
|
Term
| 132. What is the 4th step? |
|
Definition
|
|
Term
| 133. What is the 5th step? |
|
Definition
| 133. Reduction of double bond using NADPH |
|
|
Term
| 134. How is the malonyl CoA transferred to AcetylCoA? |
|
Definition
| 134. CH2 group binds to carbonyl of acetyl group forming B-keto intermediate |
|
|
Term
| 135. What happens after malonyl CoA transfer? |
|
Definition
| 135. Reduction using NADPH to form hydroxyl on w-1 ketone to form hydroxylàdehydrationàreduction using NADPH againà now chain is saturated |
|
|
Term
| 136. Beginning with Acetyl CoA and malonyl CoA what is the reaction to form palmitate? |
|
Definition
| 136. AcetylCoA+7 malonyl CoA+14NADPHàpalmitate +7CO2+7NADP+8CoA |
|
|
Term
| 137. Beginning with ACetylCoA only? |
|
Definition
| 137. Have to form Malonyl CoA’s à need 7 ATP’s in addition and 7 CO2’s to what is in the answer to #137 |
|
|
Term
| 138. How long of a chain does FA synthase produce? |
|
Definition
|
|
Term
| 139. Where does further elongation occur? |
|
Definition
|
|
Term
| 140. What is different about the elongation rx. Vs. FA synthase? |
|
Definition
| 140. Elongation occurs while FA is bound to CoA rather than ACP |
|
|
Term
| 141. What is the most common elongation rx.? |
|
Definition
| 141. Stearate from palmitate |
|
|
Term
| 142. Where are desaturases for FA located? |
|
Definition
|
|
Term
| 143. What kind of system does desaturases use for electron transfer in FA desaturation? |
|
Definition
| 143. Iron sulfur centers using cyt b5 and cyt b5 reductase, inserts double bound at d9 (ex. Oleate from stearate) |
|
|
Term
| 144. Can desaturases add double bond to carbon 12 from the alpha carbon? |
|
Definition
| 144. No, only up to carbon 10, thus why we can’t make omega-3 and omega-6 FA’s (counting from opposite end) |
|
|
Term
| 145. What are some functions of eicosanoids? |
|
Definition
| 145. Regulators of cell fxn, hormones |
|
|
Term
| 146. Describe three types of local hormones produced by eicosanoids |
|
Definition
| 146. Prostaglandin (PG), thromoxanes(TX), Leukotrienes (LT) |
|
|
Term
| 147. What is the main precursor to PG’s? What are two other minor precursors? |
|
Definition
| 147. Arachidonic acid; Eicosatrienoicacid (gamma linoleic acd) & eicosapentaenoic acid |
|
|
Term
| 148. What enhances aggregation of PGE2 and PGI2 from endothelial cells to inhibit bleeding? |
|
Definition
|
|
Term
| 149. What are some functions of Eicosanoids (6)? |
|
Definition
| 149. Inflammatory response, smooth muscle contraction, water and sodium excretion, blood pressure regulation, constrictors and dilators of BV, bronchoconstriction & bronchodilation |
|
|
Term
| 150. What bonds are unsatured in arachidonic acid? |
|
Definition
|
|
Term
| 151. What are precursors of Eicosanoids derived from? |
|
Definition
|
|
Term
| 152. Eicosanoids are produced from ____________ phospholipids. |
|
Definition
|
|
Term
| 153. What enzyme activates arachidonic acid (Ara) ? |
|
Definition
| 153. Phospholipase A2 (or PLC) |
|
|
Term
| 154. What is the regulated control step of eicosanoid synthesis? |
|
Definition
| 154. Release of Ara from membrane via PLA2 or PLC |
|
|
Term
| 155. What are the two activities of prostaglandin synthase? |
|
Definition
| 155. Cyclooxygenase, peroxidase |
|
|
Term
| 156. What does prostaglandin synthase make from Ara? |
|
Definition
|
|
Term
| 157. What is the major branch point in Eicosanoid synthesis? |
|
Definition
|
|
Term
| 158. What determines which eicosanoid will be made? |
|
Definition
| 158. Cell signaling, which cell synthesis is taking place in(IE: plateletsàthromboxane, endothelial cells PGE2,PGI2 which inhibit platelet aggregation) |
|
|
Term
| 159. What drug inhibits PG synthesis? |
|
Definition
| 159. Aspirin via cyclooxygenase enzyme (COX) |
|
|
Term
| 160. What does lipooxygenase form via Ara? |
|
Definition
|
|
Term
| 161. What does cytP450 form via Ara? |
|
Definition
|
|
Term
| 162. What is the control point for making eicosanoids? |
|
Definition
| 162. Release of Ara from membrane (TQ) |
|
|
Term
| 163. What are potential stimuli for releasing Ara from membrane? |
|
Definition
| 163. Epi, thrombin, AGII which activate PLA2 and other lipases |
|
|
Term
| 164. T or F: Eicosanoids derive from omega 6 and omega 3 FA’s |
|
Definition
|
|
Term
| 165. Describe the three main pathways for metabolism of arachidonic acid |
|
Definition
| 165. COXàPG’s, Thromboxanes; Lipoxygenase àHPETEàLeukotrienes,HETE,Lipoxins; CytP450àEpoxides(diHETE, HETE) |
|
|
Term
| 166. What does HETE stand for? |
|
Definition
| 166. Hydroxyeicosatetraenoic aid |
|
|
Term
| 167. Do eicosanoids have a long lifetime? |
|
Definition
|
|
Term
| 168. What is the mechanism of PGE,PGD,PGI? |
|
Definition
|
|
Term
| 169. What is the mechanism of PGF2 &TXA2? |
|
Definition
|
|
Term
| 170. What is the parent compound of PG’s? |
|
Definition
|
|
Term
| 171. What is the most oxidized PG? What is the 2nd most? |
|
Definition
| 171. PGA, PGB (alphabetical order from most oxidized to most reduced) |
|
|
Term
| 172. What does the 3 in PGA3 mean? |
|
Definition
|
|
Term
| 173. Describe the structure of a PG |
|
Definition
| 173. Pentyl ring with 2 acyl chains |
|
|
Term
| 174. What constituents are on the pentyl ring at positions X and Y (C9 and C11) |
|
Definition
| 174. Hydroxyl or keto group |
|
|
Term
| 175. Where is the carboxyl group located on PG? |
|
Definition
|
|
Term
| 176. What does C15 contain on PG’s? |
|
Definition
|
|
Term
| 177. What are the functions of PGI2, PGE2, and PGD2? |
|
Definition
| 177. Vasodilation, cAMP, decreases platelet aggregation, leukocyte aggregation, IL-1, IL-2 and T cell proliferation & lymphocyte migration |
|
|
Term
| 178. What is the function of PGF2α? |
|
Definition
| 178. Vasoconstriction, bronchoconstriction, smooth muscle contraction |
|
|
Term
| 179. What is released from platelets at wounds (relating to this lecture)? |
|
Definition
| 179. Thromboxane A2 (TXA2) |
|
|
Term
| 180. What is the parent compound of other PG’s? |
|
Definition
|
|
Term
| 181. What provides reducing power for the peroxidase activity of prostaglandin synthase? |
|
Definition
| 181. Glutathione (GSSG,GSH) |
|
|
Term
| 182. If you were treating pulmonary hypertension what PG would you use? |
|
Definition
|
|
Term
| 183. What are some PG’s & thromboxanes that PGH2 gives rise to? |
|
Definition
| 183. PGI2, prostacyclin, thromboxanes, PGF2alpha |
|
|
Term
| 184. Is aspirin a covalent modification on PS? |
|
Definition
| 184. Yes but ibuprofen and Tylenol are not (competitive inhibitors) |
|
|
Term
| 185. What pathway forms HETES, leukotrienes, lipoxins? |
|
Definition
| 185. Lipoxygenase pathway |
|
|
Term
| 186. What is the fxn. Of lipoxygenase? |
|
Definition
| 186. Incorporate oxygen into double bond of ArA forming hydroperoxy group which isomerizes to hydroxyl |
|
|
Term
| 187. Where are leukotrienes synthesized? |
|
Definition
|
|
Term
| 188. What increases vascular permeability, T cell proliferation, eukocyte aggregation and IL-1,IL-2? |
|
Definition
|
|
Term
| 189. What increases vascular permeability and bronchoconstriction (in lipoxygenase pathway) |
|
Definition
|
|
Term
|
Definition
| 190. No extremely unstable and reduced rapidly to form HETE’s which can be converted to leukotrienes and lipoxins |
|
|
Term
| 191. What systems are compounds produced from CytP450 pathway via ArA found in |
|
Definition
| 191. Ocular, vascular, endocrine, renal (inhibit NaK ATPase) |
|
|
Term
| 192. What backbone do glycerolipids have? |
|
Definition
|
|
Term
| 193. What composes a TAG? |
|
Definition
|
|
Term
| 194. What composes a glycerophospholipid? |
|
Definition
| 194. 2 FA’s glycerol and head group |
|
|
Term
| 195. What are some examples of ether glycerolipids. |
|
Definition
| 195. Plasmalogens, platelet activating factor |
|
|
Term
| 196. What FA are significant in milk? |
|
Definition
| 196. Butyric, Capric (C4 and C10) |
|
|
Term
| 197. What are fxn. Of TAG? |
|
Definition
| 197. Transport and store FA |
|
|
Term
| 198. What is the action of pancreatic lipase? |
|
Definition
| 198. Hydrolyze TAG to DAG and 2MG |
|
|
Term
| 199. What is the chemical structure of bile salts? |
|
Definition
| 199. Modified Cholesterol |
|
|
Term
| 200. Where are TG resynthesized? |
|
Definition
| 200. Intestinal epithelial cells |
|
|
Term
| 201. What do chylomicrons contain? |
|
Definition
| 201. Cholesterol, phospholipids, TAG |
|
|
Term
| 202. What is an intermediate in TG synthesis? |
|
Definition
|
|
Term
| 203. Can Adipose tissue directly phosphorylate glycerol? |
|
Definition
| 203. No, it does not have glycerol kinase |
|
|
Term
| 204. How does adipose tissue produce glycerol 3 phosphate? |
|
Definition
|
|
Term
| 205. Describe formation of a TAG |
|
Definition
| 205. Glycerol 3 phosphate formedàaddition of FA’s via glycerophosphate acyltransferase using FaCoA as substrateàphosphatidic acid is cleaved to add final FaCoA (TG synthetase complex is bound to ER) |
|
|
Term
| 206. Is LPL secreted in response to glucagon? |
|
Definition
| 206. No, in response to insulin |
|
|
Term
| 207. Where does PLA1 cleave? PLA2? PLC? PLD? |
|
Definition
| 207. Ester linkage of first acyl chain, ester linkage of 2nd acyl chain, phosphate group linkage to C3, phosphate linkage to head group |
|
|
Term
| 208. What are two different ways to add head groups to phosphatidic acid? |
|
Definition
| 208. Activated head group (CDP-head group) or activated DAG (CDP-DAG) |
|
|
Term
| 209. What are some examples of head group addition using activate head groups? |
|
Definition
| 209. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine |
|
|
Term
| 210. What are some examples of head group addition using activated DAG? |
|
Definition
| 210. Phosphatidylinositol, cardiolipin, phosphatidylglycerol |
|
|
Term
| 211. Is the conversion of phosphatidylserine to phosphatidylethanolamine reversible? |
|
Definition
|
|
Term
| 212. What forms cardiolipin? |
|
Definition
| 212. CDP-DAG being joined with P-Glycerol to form diphosphatidylglycerol |
|
|
Term
| 213. What can CDP-DAG also form? |
|
Definition
| 213. PIP2, and phophsatidylinositol |
|
|
Term
| 214. What is the main component of surfactant? |
|
Definition
| 214. Dipalmitoylphosphatidylcholine (reduces surface tension) |
|
|
Term
| 215. Can P lipid metabolism release ArA? |
|
Definition
| 215. Yes—a precursor to eicosonaoids |
|
|
Term
| 216. What class of glycerolipids are plasmalogens in? |
|
Definition
|
|
Term
|
Definition
| 217. Ether glycerolipids, causes platelet aggregation, edema and hypotension |
|
|
Term
| 218. Describe formation of ether glycerolipid |
|
Definition
| 218. Ether chain replaces ester chain on DHAP with alkyl substituent extension, activated headgroup then added on at expense of phosphate groupàreduce alkyl chain using NADP àplasmalogen produced |
|
|
Term
| 219. What is 2-acetyl and 1-alkyl derivative of ethanolamine plasmalogen (saturated alkyl chain) |
|
Definition
| 219. Platelet activating factor (remember it has a 2-acetyl group!) |
|
|
Term
| 220. In summary, what does ether glycerolipid synthesis require (list of items)? |
|
Definition
| 220. NADPH,AylCoA, DHAP, activate ethanolamine |
|
|
Term
| 221. Give some examples of sphingolipids |
|
Definition
| 221. Sphingomyelin, cerebrosides, sulfatides, globosides, gangliosides |
|
|
Term
| 222. How is a FA attached to a sphingosine backbone? |
|
Definition
|
|
Term
| 223. What is the difference between sphingolipids, glycolipid, and ceramides? |
|
Definition
| 223. Sphingolipids have a p-choline group, glycolipids have carbohydrate group, ceramides don’t have a group |
|
|
Term
| 224. What is a sphingolipid that forms the backbone of all other classes of sphingolipids? |
|
Definition
|
|
Term
| 225. Describe ceramide synthesis |
|
Definition
| 225. Palmitoyl coa +serineàsphingosineàreduction using NAPDH àdihydrosphingosineàFaCoAà oxidation to form double bond using FADàceramide |
|
|
Term
| 226. T or F: glycolipids are a component of cell membranes |
|
Definition
|
|
Term
| 227. Glycolipids have a _______ backbone with ________ groups attached. |
|
Definition
| 227. Ceramide, carbohydrate |
|
|
Term
| 228. What makes ceramide into sphingomyelin? |
|
Definition
| 228. Pshophocholine attachment |
|
|
Term
| 229. What tissues are glycolipids and sphingomyelin found in (mainly)? |
|
Definition
|
|
Term
| 230. What are some disease states associated with glycolipid/sphingomyelin degradation? |
|
Definition
| 230. Gauchers,Tay Sachs, Fabray’s (CNS symptoms) |
|
|
Term
| 231. Do glycolipids contain a phosphate group? |
|
Definition
|
|
Term
| 232. What are ceramide-gal called? Ceramide-glc? Ceramide-glc-gal? |
|
Definition
| 232. Galactocerebrosies, glucocerebrosides, lactosyl-ceramide |
|
|
Term
| 233. Are acidic glycolipids charged at neutral pH? |
|
Definition
|
|
Term
| 234. What do acidic glycolipids contain? |
|
Definition
| 234. N-acetylneuraminic aid (NANA) |
|
|
Term
| 235. What is an example of a ganglioside? |
|
Definition
| 235. Ceramide-glc-gal, GM1,GM2 |
|
|
Term
| 236. Where does synthesis of glycolipids take place? |
|
Definition
| 236. ER and Golgi (Sequentially adds glycosyl residues, sulfate transferred from PAPs) |
|
|
Term
| 237. How are sugars activated to attach to glycolipids? |
|
Definition
| 237. UDP or CMP head groups |
|
|
Term
| 238. Where does degradation of sphingolipids occur? |
|
Definition
|
|
Term
| 239. What is a disease caused by absence of hexoaminidase A? |
|
Definition
| 239. Tay Sach’s (GM2 ganglioside accumulates, neurodegeneration, common in Ashkenazi jews) |
|
|
Term
| 240. What is a gangliosidose caused by deficiency in Beta-glucosidase? |
|
Definition
| 240. Gauchers (glucocerebroside accumulates, Autosomal recessive) |
|
|
Term
| 241. What is a gangliosidose caused by deficiency in alpha-galactosidase A? |
|
Definition
| 241. Fabry’s (x-linked recessive, accumulation of globsides[trihexosylceramide], kidney, heart failure, burning pain in lower extremeties) |
|
|
Term
| 242. What is cholesterol a precursor for? |
|
Definition
| 242. Bile acids, steroid formation, vitamin D, etc. |
|
|
Term
| 243. T or F: cholesterol plays a role in artherosclerosis/gallstones. |
|
Definition
|
|
Term
| 244. What dietary products contain cholesterol listed in lecture? |
|
Definition
|
|
Term
| 245. What is most of cholesterol esterfied to in the circulation? |
|
Definition
|
|
Term
| 246. What is the majority of cholesterol delivered to the small intestine from ? |
|
Definition
| 246. Biliary cholesterol (800-1200mg/day) |
|
|
Term
| 247. How much cholesterol is absorbed from the small intestine? |
|
Definition
|
|
Term
| 248. Where are Biliary cholesterol molecules synthesized? |
|
Definition
|
|
Term
| 249. How is circulating cholesterol transported? |
|
Definition
| 249. In lipoproteins with cholesterol on surface and cholesteryl esters in the core |
|
|
Term
| 250. What is the cholesterol transporter of the small intestine? |
|
Definition
|
|
Term
| 251. What helps reflux cholesterol back into the small intestinal lumen and excludes plant sterols from entering chylomicrons? |
|
Definition
|
|
Term
| 252. What esterfies cholesterol for transport into chylomicrons? |
|
Definition
|
|
Term
| 253. What puts cholesterols in chylomicrons? |
|
Definition
|
|
Term
| 254. What is the secondary structure of ABCG5/ABCG8? |
|
Definition
|
|
Term
| 255. T or F: ABCG8 and ABCG5 are transcribed in the same direction |
|
Definition
|
|
Term
| 256. What would a mutation in ABCG8/ABCG5 lead to? |
|
Definition
| 256. Inability to exclude plant sterols |
|
|
Term
| 257. Where is the maximum expression of NPC1L1 |
|
Definition
|
|
Term
| 258. What drug inhibits NPC1L1? |
|
Definition
|
|
Term
| 259. What OTC substance can we use to increase dietary sterols and inhibit cholesterol absorption thereby lowering plasma cholesterol? |
|
Definition
|
|
Term
| 260. What is the initial substrate for cholesterol synthesis? |
|
Definition
|
|
Term
| 261. Describe briefly, cholesterol synthesis |
|
Definition
| 261. Acetyl coa àacetoacetyl CoA via acetyl CoA thiolaseà3-hydroxy-3methylgutaryl CoA (HMG CoA) via HMG CoA synthaseàMevalonate via HMG CoA reductase (regulated, commited step) using 2NADPHà3 mevalonates form farnesyl pyrophosphate via a series of stepsà2 farnesyl pyrophosphates joined to make squalene (30 carbon precursor)àvarious decarboxylations etc. to make dcholesterol (27 carbon) |
|
|
Term
| 262. What is the total cost of cholesterol synthesis? |
|
Definition
| 262. 18 moles Acetyl CoA, 36 moles ATP, 16 moles NADPH |
|
|
Term
| 263. How many carbons does cholesterol have? |
|
Definition
|
|
Term
| 264. What is the rate limiting step of cholesterol synthesis? |
|
Definition
|
|
Term
| 265. What are some factors that effect HMG CoA reductase? |
|
Definition
| 265. Insulin (+), glucagon (-), thyroid hormone (+), cortisol (-), intracellular HMG CoA reductase levels, and intracellular cholesterol levels |
|
|
Term
| 266. What class of drugs inhibits HMG CoA reductase? |
|
Definition
|
|
Term
| 267. What receptor regulates cholesterol synthesis and storage? |
|
Definition
|
|
Term
| 268. What is the function of LXR’s? |
|
Definition
| 268. Put cholesterol in a safer place by transcriptional regulation of key intermediates/enzymes (avoids cholesterol overload) |
|
|
Term
| 269. What activates LXR’s? |
|
Definition
|
|
Term
| 270. What do LXR’s heterodimerize with? |
|
Definition
| 270. RXR (retinoid X receptor) |
|
|
Term
| 271. What do oxysterols indicate? |
|
Definition
| 271. Amount of free cholesterol |
|
|
Term
| 272. Is NPC1L1 upregulated by LXR’s? |
|
Definition
| 272. No, downregulated (takes less cholesterol up) |
|
|
Term
| 273. Are CYP7A and ABCG5/ABCG8 upregulated by LXR’s? |
|
Definition
|
|
Term
| 274. What are some complications of therapeutic LXR activation? |
|
Definition
| 274. Hypertryglyceridimia, enhanced cholesterol esterification and storage, apoptosis and inflammation |
|
|
Term
| 275. What is the purpose of LXR’s upregulating HDL’s? |
|
Definition
| 275. Return cholesterol from peripheral tissues to liver |
|
|
Term
| 276. What syndrome is associated with 3-beta-delta-7hydroxylase deficiency? |
|
Definition
| 276. Smith-lemli-opitz syndrome |
|
|
Term
| 277. What are some characteristics of the answer to #276? |
|
Definition
| 277. High plasma 7-dehydrocholesterol which is toxic, mental retardation and multiple congenital malformations |
|
|
Term
| 278. How can we treat the answer to #276? |
|
Definition
| 278. Feed cholesterol which can feedback inhibit HMG CoA reductase, or use statins |
|
|
Term
| 279. In infants what AA is conjugated to bile acids? Adults? |
|
Definition
|
|
Term
| 280. What are the two primary bile acids listed in class? |
|
Definition
| 280. Taurocholic acid, taurchenodeoxycholic acid |
|
|
Term
| 281. How much bile acids are excreted per day? |
|
Definition
|
|
Term
| 282. What are the three components that give us a critical micellar concentration? |
|
Definition
| 282. Cholesterol, lecithin, bile salts |
|
|
Term
| 283. What is the precursor for all steroid hormones? |
|
Definition
|
|
Term
| 284. Where are glucocorticoids produced ? mineral corticoids? Sex hormones? |
|
Definition
| 284. Zona fasciulata, reticularis; zona glomerulosa; testes and ovary |
|
|
Term
| 285. What is the most potent gluccocorticoid? What are some of its effects? |
|
Definition
| 285. Cortisol, anti inflammatory, stimulates GNG, sodium retention |
|
|
Term
| 286. What senses drop in ECFV and causes release of renin? |
|
Definition
| 286. Juxtaglomerular apparatus (JGA) |
|
|
Term
| 287. Where is testsosterone produced? Estrogen? |
|
Definition
| 287. Leydig cells, ovarian granulose cells |
|
|
Term
| 288. Does testosterone increase muscle mass? |
|
Definition
|
|
Term
| 289. What is the main defect in congenital adrenal hyperplasia? |
|
Definition
| 289. 21-beta-hydroxylase deficiency (deficiency in mineralcorticoids and glucocorticoids) less inhibition of ACTH by cortisol more shunting through pathway and more androgens produced (masculinization of female infants) |
|
|
Term
| 290. Describe briefly, vitamin D synthesis |
|
Definition
| 290. Converted to vitamin D3 from 7dehydroxy cholesterol in malpighian layer of skinàundergoes hydroxylation at C25 in liver and C1 in kidney to form 1,25 dihydroxycholecaciferol |
|
|
Term
| 291. What are some effects of vitamin D? |
|
Definition
| 291. Increased absorption of calcium by transcriptional regulation of enzymes, recruits stem cells to make osteoclasts, absorbs calcium and phosphate more readily in the intestine |
|
|
Term
| 292. What is the major inducer of 1-alpha hydroxylase |
|
Definition
| 292. PTH which is induced by low calcium |
|
|
Term
| 293. What can also stimulate induction of 1-alpha hydroxylase directly? |
|
Definition
| 293. Hypocalcemia and hypophosphatemia |
|
|
Term
| 294. What can vitamin D deficiency lead to ? |
|
Definition
| 294. Rickets in children and osteomalacia in adults |
|
|
Term
| 295. What is the purpose of a lipoprotein? |
|
Definition
| 295. Provide a thermodynamically stable particle to transport lipid through bloodstream |
|
|
Term
| 296. What kind of lipoproteins are present in the liver? |
|
Definition
|
|
Term
| 297. What kind of lipoproteins are present in the intestine? |
|
Definition
| 297. CM, small amounts of vldl, hdl |
|
|
Term
| 298. Which lipoprotein is the largest in size? |
|
Definition
|
|
Term
| 299. Which lipoprotein transports most of the cholesterol? |
|
Definition
|
|
Term
| 300. What are surface peptides of lipoprotein particles with lipid binding properties? |
|
Definition
|
|
Term
| 301. What role do apolipoproteins have? |
|
Definition
| 301. Assembly,secretion, peripheral metabolism and clearance of lipoproteins |
|
|
Term
| 302. What are the functions of ApoB-100? |
|
Definition
| 302. From liver, essential for VLDL packaging and secretion (contains LDLR domain) |
|
|
Term
| 303. What are the functions of ApoB-48? |
|
Definition
| 303. Intestinal form, essential for CM packing and secretion, lacks LDLR |
|
|
Term
| 304. What is the function of Apo A-1? |
|
Definition
| 304. Major apolipoprotein of HDL, co factor for LCAT which esterfies free cholesterol into HDL’s |
|
|
Term
| 305. How is the mRNA for Apo-B edited in making B-48 instead of B-100? |
|
Definition
| 305. Single base pair substation, inserts stop codon using APOBEC-1 complex that has a mooring sequence to help precisely insert A for a C |
|
|
Term
| 306. What is the function of Apo A-IV? |
|
Definition
| 306. May activate LCAT, lots of functions, decreases eating behavior, prevents artherosclerosis, packing of lipid into CM |
|
|
Term
| 307. What is the function of Apo C-II? |
|
Definition
| 307. Activates LPL which hydrolyzes TG in VLDL and CM’s |
|
|
Term
| 308. What is the function of Apo-E? |
|
Definition
| 308. Ligand for hepatic chylomicron remant receptor and LDL receptor |
|
|
Term
|
Definition
|
|
Term
| 310. What is the function of HL? |
|
Definition
| 310. Remnant lipoprotein uptake, attached to heparin sulfate PG on hepatocytes |
|
|
Term
| 311. What is the function of LCAT? |
|
Definition
| 311. Transfer of fatty acid from lecithin to free cholesterol in HDL |
|
|
Term
| 312. What activates LCAT? |
|
Definition
|
|
Term
| 313. What is the function of ABCA1/ABCG1? |
|
Definition
| 313. Mediate phospholipid/cholesterol efflux from cells to lipid poor Apo A1 in reverse cholesterol transport |
|
|
Term
| 314. What is the rate limiting step of cholesterol synthesis? |
|
Definition
|
|
Term
| 315. What is the function of ACAT? |
|
Definition
| 315. Conversion of free cholesterol to cholesterol ester |
|
|
Term
| 316. What does LDL receptor bind to? |
|
Definition
| 316. ApB-100, ApoE and LDL |
|
|
Term
| 317. What is the function of LRP? |
|
Definition
| 317. Heptake uptake of remnant CM |
|
|
Term
| 318. What is the function of SR-BI? |
|
Definition
| 318. Hepatic uptake of cholesteryl ester from HDL in reverse cholesterol transport |
|
|
Term
| 319. How does HDL take cholesterol back to the liver (enzyme)? |
|
Definition
| 319. Via SRBP1 (scavenger receptor B1) |
|
|
Term
| 320. Where are FA re-esterefied? |
|
Definition
|
|
Term
| 321. Where are CM’s assembled? |
|
Definition
|
|
Term
| 322. Where is the final processing of apolipoproteins/lipids for basolateral secretion? |
|
Definition
|
|
Term
| 323. Describe the pathway of FA from exogenous sources |
|
Definition
| 323. Intestinal epitheliumàFABPàApoB-48 àCM via MTPàPCTVàGolgiàSecretion |
|
|
Term
| 324. What transfers lipid from ER membrane to newly translated apo B ? |
|
Definition
| 324. Microsomal Triglyceride transfer protein |
|
|
Term
| 325. What is another function of MTP? |
|
Definition
| 325. Transfer bulk lipid from ER membrane to lumen for further lipoprotein particle lipidation |
|
|
Term
| 326. Is transfer of CM to Golgi via PCTV microtubule dependent? |
|
Definition
|
|
Term
| 327. Is transfer of CM from golgi to BLM microtubule dependent? |
|
Definition
|
|
Term
| 328. Describe Exogenous CM metabolism |
|
Definition
| 328. CM from intestines w/ApoB-48àE and CII attach and activate LPL, CII recycled to HDLàchylomicron remnants into Liver |
|
|
Term
| 329. Describe Endogenous CM metabolism |
|
Definition
| 329. ApoB-100 CMàLDL to release FA, cholesterol recycled via ABCG1/A1 |
|
|
Term
| 330. Describe reverse cholesterol transport |
|
Definition
| 330. SRB1 removes cholesterol and stores in hepatocyteàABCA1/ApoA1 form pre beta HDL which takes up cholesterol from peripheral tissues (ABCA1/G1 fxn) and esterfies cholesterol and HDL molecules via LCAT for transfer back to liver |
|
|
Term
| 331. What is the role of SREBP? |
|
Definition
| 331. Bound to SCAP which measures concentration of oxytrols (indicator of cholesterol) when cholesterol is low SREBP is released and LDLR’s are upregulated, leads to increase in cholesterol levels in the cell |
|
|
Term
| 332. What levels indicate risk for cholesterol? |
|
Definition
|
|
Term
| 333. Total cholesterol =300 mg/dL, HDL= 100 , TG=100, what is LDL (mg/dL) |
|
Definition
|
|
Term
| 334. Total cholesterol =300 mg/dL, HDL= 100 , TG=100, what is LDL (mmol/L) |
|
Definition
|
|
Term
| 335. Do lifestyle changes effect monogenic dyslipidemia’s? |
|
Definition
| 335. Typically not, most require drug therapy, whereas polygenic is opposite |
|
|
Term
| 336. What is the defect in familial hypercholesterolemia? Familial combined hyperlipidemia? Familial dysbetalipoproteinemia? |
|
Definition
| 336. LDL receptor, overproduction ApoB100, E2/E2 isoform defective remnant binding to LDL receptor |
|
|
Term
| 337. Elevalated levels of Apo (a) and Lp (a) are associated with what? |
|
Definition
| 337. Promoting clot formation on atherosclerotic plaques (LDL bound to ApoA looks like kringles) |
|
|
Term
| 338. Describe the mechanism of atherosclerosis |
|
Definition
| 338. DamageàLDL enters through broken epitheliumàLDL is oxidizedàadhesion factors expressed & monocytes bindàMacrophages have scavenger receptor to bind oxidized LDL & internalizes itàMacrophage becomes overloaded with LDL and is now called foam cellàcytokines etc. form plaque on endothelial layer & produce metalloproteinases that can break down collagen, platelets bind and initiate thrombus that can cause MI |
|
|
Term
| 339. T or F: A stable atherosclerotic plaque has a thin fibrous cap. |
|
Definition
|
|
Term
| 340. What are the purines? Pyrimidines? |
|
Definition
| 340. Purines: AG, Pyrmidines: TC |
|
|
Term
| 341. What are some functions of nucleotides/sides? |
|
Definition
| 341. Nucleic acids, energy metabolism, cellular 2nd messengers,etc. |
|
|
Term
| 342. What is the difference between a nucleotide and nucleoside? |
|
Definition
| 342. Nucleotide has phosphate groups, side does not |
|
|
Term
| 343. What is the precursor of AMP and GMP? |
|
Definition
|
|
Term
| 344. What signals in the purine synthesis pathway can stimulate cell division? |
|
Definition
| 344. Diadenosyl tetraphosphate, diadenosyl triphosphate |
|
|
Term
| 345. What is the first step in the purine de novo pathway? |
|
Definition
| 345. Production of PRPP from ribose 5 phosphate using PRPS1/PRPS2 (requires ATP) |
|
|
Term
| 346. Is this step regulated? |
|
Definition
| 346. Yes, allosterically by ADP/GDP |
|
|
Term
| 347. What is the second step in the pathway? |
|
Definition
| 347. RPP to 5-phosphoribosyl-1amine using GPAT, this is the commited step, also inhibited by ADP/GDP |
|
|
Term
| 348. What is the commited step in purine synthesis? |
|
Definition
|
|
Term
| 349. What is the 3rd step of purine synthesis? |
|
Definition
| 349. GAR synthetase to add glycine onto phosphoribosyl amine to make GAR |
|
|
Term
| 350. What step adds aspartate to CAIR? |
|
Definition
|
|
Term
| 351. In the following step after SAICAIR what TCA intermediate is produced? |
|
Definition
| 351. Fumarate (from the aspartate added on) |
|
|
Term
| 352. Where do the carbons from purines derive from? |
|
Definition
| 352. Glutamine, glycine (largest contribution), aspartate |
|
|
Term
| 353. What enzyme forms AMP from Inosinate by releasing fumarate? |
|
Definition
| 353. Adenylosuccinate lyase (ADSL) |
|
|
Term
| 354. What do deficiencies in the gene for ADSL cause? |
|
Definition
| 354. Succinylpurinemic autism |
|
|
Term
| 355. What is the rate limiting step in GMP synthesis? |
|
Definition
|
|
Term
| 356. How many ATP equivalents to make GMP? AMP? |
|
Definition
| 356. 8 and 7 respectively |
|
|
Term
| 357. In making GMP is ATP or GTP used in GMP synthetase? |
|
Definition
| 357. ATP (to keep the balance of ATP/GTP similar in vivo) |
|
|
Term
| 358. What enzymes phosphorylate AMP/GMP? |
|
Definition
| 358. Adenylate kinase, guanylate kinase |
|
|
Term
| 359. What enzymes phosphorylate nucleoside diphosphate? |
|
Definition
| 359. Nucleoside diphosphate kinase |
|
|
Term
| 360. What inhibits formation of AMP? GMP? |
|
Definition
| 360. AMP and GMP respectively (block each of their respective pathways, feedback inhibition) |
|
|
Term
| 361. What activates GPAT? |
|
Definition
|
|
Term
| 362. Describe purine degradation |
|
Definition
| 362. AMPànucleotidaseàadenosineàadenosine deaminase to inosineànucleotide phosphorylase to hypoxanthineàxanthine oxidase to xanthine and uric acid |
|
|
Term
| 363. What enzyme in purine degradation deficiency can cause SCID? |
|
Definition
| 363. Adenosine deaminase (dATP inhibits DNA synthesis and kills rapidly proliferating cells such as lymphocytes) |
|
|
Term
| 364. What other enzyme deficiency can cause SCID? |
|
Definition
| 364. Nucleoside phosphorylase (after ADA in degradative pathway, still accumulates same products) |
|
|
Term
| 365. How is AMP converted to IMP? |
|
Definition
|
|
Term
| 366. What is a deficiency in adenosine monosphate deaminase associated with? |
|
Definition
|
|
Term
| 367. What is an inhibitor of xanthine oxidase? |
|
Definition
| 367. Allopurinol (prevents uric acid from building up by instead having hypoxanthine/xanthine buildup which are more soluble), used to treat gout |
|
|
Term
| 368. How can excess bases be scavenged? |
|
Definition
| 368. HGPRT, APRT can combine PRPP with bases to form IMP,AMP,GMP |
|
|
Term
| 369. What can loss of HGPRT cause? |
|
Definition
| 369. Lesch Nyan syndrome (mental problems, biting, self mutilation) |
|
|
Term
| 370. What is the basis of this disease? |
|
Definition
| 370. Increased PRPP which activates purine synthesis |
|
|
Term
| 371. Can high levels of urate be useful to humans (evolutionarily)? |
|
Definition
| 371. Yes, prevents oxidative damage & allows us to senesce |
|
|
Term
| 372. What is an antagonist of GPAT that mimics Gln? |
|
Definition
|
|
Term
| 373. How can muscle replenish TCA intermediates via purine synthesis? |
|
Definition
| 373. Using ADA to form IMP which can be used via ASDL to produce fumarate |
|
|
Term
| 374. What are the pyrimidines? |
|
Definition
| 374. C,T,U (single ring bases) |
|
|
Term
| 375. What is the branchpoint in pyrimidine synthesis (similar to what was seen for IMP in purine synthesis)? |
|
Definition
|
|
Term
| 376. What enzyme is required to make deoxyribonucleotides? |
|
Definition
| 376. Ribonucleotide reductase |
|
|
Term
| 377. What two compounds form the pyrimidine ring primarily? |
|
Definition
| 377. Carbomoyl phosphate and aspartate |
|
|
Term
| 378. What is the regulated step for pyrimidine synthesis in Eukarya? Bacteria? |
|
Definition
|
|
Term
| 379. How many ATP’s does the CPS II rxn. use? |
|
Definition
|
|
Term
| 380. Where is CPS I used? |
|
Definition
| 380. Urea cycle in mitochondria |
|
|
Term
| 381. Where does carbomoyl phosphate get its nitrogen from? |
|
Definition
|
|
Term
| 382. What enzyme adds asparte to the pyrimidine ring? |
|
Definition
|
|
Term
| 383. Are pyrimidines synthesized on a ribose ring like purines ? |
|
Definition
| 383. No, they are synthesized then attached later |
|
|
Term
| 384. What enzyme closes the pyrimidine ring? |
|
Definition
|
|
Term
| 385. After ring closure what enzyme forms orotate from dihyrdoorotate? |
|
Definition
| 385. Dihydroorate dehydrogenase via NAD+ (which passes e- to UQ) |
|
|
Term
| 386. How is UTP converted to CTP? |
|
Definition
| 386. Amidation at 4 position using Gln (therefore can be inhibited by azaserine) |
|
|
Term
| 387. What activates ATcase? |
|
Definition
| 387. ATP (means we have enough purine, make pyrimidinesàCTP inhibits) |
|
|
Term
| 388. What inhibits CPS II? Activates? |
|
Definition
|
|
Term
| 389. Does CTP inhibit CPS II? |
|
Definition
| 389. No (this is counterintuitive) |
|
|
Term
| 390. What substrate does ribonucleotide reductase work on? |
|
Definition
|
|
Term
| 391. What hydroxyl is removed via RR? |
|
Definition
|
|
Term
| 392. Describe the flow of electrons in the RR mechanism |
|
Definition
| 392. Electrons move to RR via thioredoxin/thioredoxin reductase using sulfhydryl groups which undergo reversible oxidations to form disulfide bonds that can be reduced back to SH groups (to dump electrons into nucleotide via putting H instead of O) |
|
|
Term
| 393. Describe the structure of RR |
|
Definition
| 393. Tetramer, one active site, has specificity and activity site |
|
|
Term
| 394. What AA’s are involved in electron transfer in RR? |
|
Definition
|
|
Term
| 395. What reduces sulfhydryl groups to restore activity of RR? |
|
Definition
| 395. Thiredoxin reductase via NADPH (alternative is GSSG) |
|
|
Term
| 396. If ATP is bound to RR what does this do to the enzyme? (in its activity site) |
|
Definition
| 396. Turns it ON: basically says we are in a dividing state so we need more pyrimidine synthesis for DNA synthesis |
|
|
Term
| 397. If dATP is bound to RR what does this do? |
|
Definition
|
|
Term
| 398. What does the specificity site do? |
|
Definition
| 398. Ensures a balanced pool of nucleotides (if we have too many purines, make pyrimidines etc.) |
|
|
Term
| 399. What is thymines only function? |
|
Definition
|
|
Term
| 400. What form must cytidine be in to be a substrate for thymidylate synthesis? |
|
Definition
|
|
Term
| 401. What intermediate is used to make thymidine from cytidine |
|
Definition
|
|
Term
| 402. What inhibits thymidylate synthase? |
|
Definition
| 402. Methotrexate etc. (inhibits N5,10 THF out by causing inhibition of dihydrofolate reductase) |
|
|
Term
| 403. What is a suicide inhibitor of thymidylate synthase? |
|
Definition
| 403. Fluorodeoxyuridylate, since fluorine is very electronegative it is a poor leaving group (its valence reaches stability in the rx. mechanism) |
|
|
Term
| 404. What are some examples of methyl xanthine stimulators? |
|
Definition
| 404. Chocolate, coffee, etc. (increase cAMP by inhibiting phosphodiesterase) |
|
|
Term
| 405. What compounds can be used to inhibit nucleotide synthesis reactions that use Gln as a substrate? |
|
Definition
| 405. Azoserine, DON (GPAT,CPS II, CPT synthase etc.) |
|
|
Term
| 406. What is an inhibitor of reverse transcriptase? |
|
Definition
|
|
Term
| 407. How are all of the active sites for ATcase, dihydroorotase, dihydroorotase DH assembled? |
|
Definition
| 407. On one peptide (substrate channeling) |
|
|
Term
| 408. T or F: AA’s maintain blood pH levels |
|
Definition
|
|
Term
| 409. What are proteins that undergo extensive synthesis and degradation in reticulocytes? |
|
Definition
|
|
Term
| 410. T or F: heme has a long half life |
|
Definition
|
|
Term
| 411. T or F: collagen has a long half life |
|
Definition
|
|
Term
| 412. What are some factors affecting the rates of protein degradation? |
|
Definition
| 412. Glucocorticoids (increase degradation), thyroid hormones (protein turnover), insulin (protein synthesis), lysosomes (proteolysis), denaturation |
|
|
Term
| 413. What are 4 AA’s degraded via the ubiquitin protesome pathway? |
|
Definition
|
|
Term
| 414. Presence of what AA’s make protein unstable at N terminus? |
|
Definition
|
|
Term
| 415. What are the essential AA’s? |
|
Definition
| 415. Arg, His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val (MILK RH FTW V) |
|
|
Term
| 416. Lack of a single AA can give rise to wasting disease called? |
|
Definition
| 416. Kwashiorkor (causes edema due to increased osmotic pressure in interstitium) |
|
|
Term
| 417. What are 3 ways AA’s are absorbed? |
|
Definition
| 417. Sodium cotransport, facilitated transport, g-glutamyl cycle |
|
|
Term
| 418. What is re-converted to GSH in the g-glutamyl cycle? |
|
Definition
|
|
Term
| 419. What is hartnups disease? |
|
Definition
| 419. Inability to absorb neutral/aromatic AA’s |
|
|
Term
| 420. What are symptoms of hartnups disease? |
|
Definition
| 420. Dermatitis, diarrhea, dementia |
|
|
Term
| 421. Decrease in cysteine uptake can cause? |
|
Definition
| 421. Cystinuria via oxidation to cystine in urine |
|
|
Term
| 422. How does penicillamine alleviate cystinuria? |
|
Definition
| 422. Reacts with one Cys to form cys-penicillamine |
|
|
Term
| 423. Do pt. with hartnup or cystinuria have hyperamionacidemia? |
|
Definition
| 423. No, they do not absorb them so they are not in excess in serum |
|
|
Term
| 424. What genetic defect in AA absorption is linked with cystinuria? |
|
Definition
| 424. Defective Lys, ornithine, cysteine absorption |
|
|
Term
| 425. What are the purely ketogenic AA’s? |
|
Definition
|
|
Term
| 426. What is the compound that is excreted containing nitrogen? |
|
Definition
|
|
Term
| 427. What funnels amino groups into glutamate? |
|
Definition
| 427. Transamination reactions |
|
|
Term
| 428. Transamination moves an amino group from an AA to what? |
|
Definition
|
|
Term
| 429. What do all transaminases use to transfer amino groups? |
|
Definition
| 429. Pyridoxyl 5’ phosphate (PLP) |
|
|
Term
| 430. What does Ala + alphaketoglutarate produce via ALT ? |
|
Definition
| 430. Pyruvate and glutamate |
|
|
Term
| 431. What does glutamate and oxaloacetate produce via AST? |
|
Definition
| 431. Alphaketoglutarate and aspartate |
|
|
Term
| 432. If there is an abnormal increase in the substrates for these reactions (AST and ALT) what organ is in failure? |
|
Definition
|
|
Term
| 433. What is an enzyme that uses NADPH to produce ammonia for the urea cycle? |
|
Definition
|
|
Term
| 434. T or F: glutamate is a neurotransmitter |
|
Definition
|
|
Term
| 435. What are Asn and Gln deaminated by and what do they form from these deaminations? |
|
Definition
| 435. Asp, Glu via asparaginase and glutaminase |
|
|
Term
| 436. What enzyme deaminates aspartate? |
|
Definition
|
|
Term
| 437. What do tumor cells require for growth that can be inhibited in these pathways? |
|
Definition
| 437. Asparagine, inhibited by adding asparaginase which converts Asn to Asp |
|
|
Term
| 438. What are Ser and Thr deaminaetd by? |
|
Definition
| 438. Ser and Thr dehydratase to pyruvate & a-ketobutyrate respectively |
|
|
Term
| 439. What is the only form of nitrogen that can pass through membranes? |
|
Definition
|
|
Term
| 440. What sites in the body is NH4+ released? |
|
Definition
|
|
Term
| 441. If the liver is damaged would NH3 levels rise? |
|
Definition
| 441. Yes without urea cycle it would accumulate |
|
|
Term
| 442. How is urea in plasma measured? |
|
Definition
| 442. Blood urea nitrogen (BUN), typically 8-20mg/dl |
|
|
Term
| 443. What can excess NH3 do to the body? |
|
Definition
| 443. Ammonia can be made into glu which can deplete brain of alphaketoglutarate causing OAA to fall and TCA to stopàcell dmg; increased Glu can lead to Gln formation which depletes Glu and GABA (NT’s); brain swelling due to osmotic pressure |
|
|
Term
| 444. What enzyme in the Urea cycle adds nitrogen onto bicarbonate? |
|
Definition
|
|
Term
| 445. What enzyme adds carbomyl onto ornithine? |
|
Definition
| 445. Ornithine transcarbamolase |
|
|
Term
| 446. Where are the 2 enzymes aforementioned located? |
|
Definition
|
|
Term
| 447. What is the 3rd step in the urea cycle? |
|
Definition
| 447. Arginnosuccinate synthetase to form Argininosuccinate from asprate and citrulline |
|
|
Term
| 448. What is the 4th step? |
|
Definition
| 448. Arginnosuccinase to cleave fumarate from argininosuccinate |
|
|
Term
| 449. What is the 5th step? |
|
Definition
| 449. Arginase to cleave urea off argininosuccinate and produce ornithine (cycle is complete) |
|
|
Term
| 450. Where do steps 3-5 take place? |
|
Definition
|
|
Term
| 451. What is the overall reaction eqn. for urea cycle? |
|
Definition
| 451. NH4+bicarbonate+amino group of Asp+ATPàurea+fumarate+ADP+AMP+PPi |
|
|
Term
| 452. How are the TCA and urea cycle linked? |
|
Definition
| 452. Via fumarate and alphaketoglutarate |
|
|
Term
| 453. How is most nitrogen carried in blood? |
|
Definition
|
|
Term
| 454. Name two sources for NH3 in urea cycle |
|
Definition
| 454. Glutamine via glutaminase, alanine via ALT |
|
|
Term
| 455. What is the alanine cycle? |
|
Definition
| 455. Glu in muscle transaminated to Ala which is transferred to liver and converted to pyruvate for further metabolism |
|
|
Term
| 456. What type of hyperammonemia is genetic and most severe? |
|
Definition
|
|
Term
| 457. What type is late onset with liver cirrhosis? |
|
Definition
|
|
Term
| 458. What is an activator of CPS I? |
|
Definition
|
|
Term
| 459. What synthesizes the answer to #458? |
|
Definition
| 459. N-acetyl glutamate synthetase (NAGS) |
|
|
Term
| 460. What will a defect in NAGs lead to? |
|
Definition
| 460. Type 1 hyperammonemia |
|
|
Term
| 461. How can we treat hyperammonemia? |
|
Definition
| 461. Benzoate, pheylacetateàremoves gly and Gln causes cell to utilize NH3 to resynthesize them |
|
|
Term
| 462. What are some characteristics of OTC deficiency? |
|
Definition
| 462. Increased carbomoyl phosphate, increased orotic acid (via CPSII in purine synthesis) |
|
|
Term
| 463. What is treatment for argininosuccinase deficiency? |
|
Definition
| 463. Increased arginine, reduced protein intake |
|
|
Term
| 464. What converts urea to carbonic acid and ammonia? |
|
Definition
| 464. Urease generated by bacterium proteus mirabilis |
|
|
Term
| 465. What is ppt’d as kidney stones? |
|
Definition
| 465. Magnesium ammonium phosphate |
|
|
Term
| 466. Where is the nitrogen in urea derived from? |
|
Definition
| 466. Aspartate and ammonia |
|
|
Term
| 467. What are some treatments for urea cycle enzymes? |
|
Definition
| 467. Low protein intake (replace with a-ketoacids), remove excess ammonia by using levulose to kill ammonia producing bacteria, administer sodium benzoate,etc. |
|
|
Term
| 468. What is the only tissue that has all the pathways for amino acid synthesis and degradation? |
|
Definition
|
|
Term
| 469. What are all 20 AA’s able be broken down into? |
|
Definition
| 469. AcetylCoA, pyruvate, 4 TCA intermediates (OAA, fumarate, succinylCoA, alphaketoglutarate) |
|
|
Term
| 470. What is a ketogenic AA? |
|
Definition
| 470. Can be made into AcetylCoA or acetoacetate |
|
|
Term
| 471. What is a glucogenic AA? |
|
Definition
| 471. Can be made into glucose |
|
|
Term
| 472. What are the purely ketogenic AA’s? |
|
Definition
|
|
Term
| 473. What are the ketogenic/glucogenic AA’s? |
|
Definition
|
|
Term
| 474. Describe the pathway of glycine synthesis |
|
Definition
| 474. Pyruvateàserineàglycine via PLP and THFàGly |
|
|
Term
| 475. During glycine synthesis what is a methyl group transferred to that can form carbon dioxide and ammonium ion? |
|
Definition
|
|
Term
| 476. By enzymatic action of an oxidase what can glycine become? |
|
Definition
|
|
Term
| 477. What is the condition caused by defective transaminase in Gly metabolism? |
|
Definition
| 477. Oxaluria type I (due to less conversion of glyoxylate back to Gly and accumulation of glyoxylate) |
|
|
Term
| 478. What is a clinical condition manifested by excess glyoxylate |
|
Definition
| 478. kidney stones (ppt. with calcium) |
|
|
Term
| 479. Degradation of what other AA other than Ser can generate Gly? |
|
Definition
|
|
Term
| 480. In cysteine metabolism where does the sulfur originally come from? |
|
Definition
|
|
Term
| 481. Met is degraded to generate what product (via methyltransferase) |
|
Definition
|
|
Term
| 482. What intermediate is used in Met degradation for methyl transfer? |
|
Definition
|
|
Term
| 483. What can homocysteine be then converted into? |
|
Definition
| 483. Back to Met or into cysteine via cystathionase |
|
|
Term
| 484. What can cysteine be degraded to? |
|
Definition
| 484. Sulfinic acid, in presence of alpha ketoglutarate it can be degraded to pyruvate (thus it is a glucogenic AA) |
|
|
Term
| 485. The sulfhydryl groups of cysteine can be oxidized to form what which generate sulfated proteoglycans |
|
Definition
|
|
Term
| 486. Can cysteine inhibit cystathionase via feedback inhibition? |
|
Definition
|
|
Term
| 487. What does a deficiency in cystathionase lead to? |
|
Definition
| 487. Cystathionuria (benign disorder) |
|
|
Term
| 488. What could cause a deficiency in cystathionase? |
|
Definition
| 488. Dietary deficiency of pyridoxine(Vit. B6) or Vit. B12 |
|
|
Term
| 489. What does a deficiency in cystathionine synthase cause? |
|
Definition
| 489. Homocystinemia/Homocystinuria (accumulation of homocysteine and met in brain, can cause loss in cognitive fx. , tall stature, CV disease, thrombi, emboli, etc.) |
|
|
Term
| 490. What is the treatment for homocystinuria? |
|
Definition
| 490. Low met diet, high doses of pyridoxine |
|
|
Term
| 491. Can our bodies synthesize aromatic rings? |
|
Definition
| 491. No (makes them essential AA’s) |
|
|
Term
| 492. How is tyrosine synthesized? |
|
Definition
| 492. From Phe via hydroxylation reaction using oxygen and tetrahydrobiopterin |
|
|
Term
| 493. T or F: Any defective step in Phe or Tyr synthesis causes severe diseases |
|
Definition
|
|
Term
| 494. What does a deficiency in Phe hydroxylase present as? |
|
Definition
| 494. Phenylketouia (PKU), phenylpyruvate accumulates and is excreted (mental retardation, lighter skin due to impaired tyrosine synthesis) |
|
|
Term
| 495. What is the treatment for PKU? |
|
Definition
| 495. Diet low in Phe, rich in Tyr |
|
|
Term
| 496. What is the first step in degradation of tyrosine? |
|
Definition
| 496. Removal of ammonia via tyrosine aminotransferase |
|
|
Term
| 497. What does a defect in this step cause? |
|
Definition
| 497. Tyrosinemia II (eye, skin, lesions, neurological disorders) àlow tyr and low phe diet is treatment |
|
|
Term
| 498. What does deficiency in homogentisate oxidase cause? |
|
Definition
| 498. Alcaptonuria (accumulation of homogentisate which causes arthritis) |
|
|
Term
| 499. What does a deficiency in degradation of fumarylacetoacetate cause? |
|
Definition
| 499. Tyrosinemia I (liver failure and death within 1 yr of life) |
|
|
Term
| 500. Where does the aromatic ring of Trp end up via degradation pathways? |
|
Definition
|
|
Term
| 501. Where does the carbon skeleton of Trp end up? |
|
Definition
|
|
Term
| 502. Trp to NAD requires what cofactor? What does a deficiency in this cofactor cause? |
|
Definition
| 502. PLP, pellagra like symptoms |
|
|
Term
| 503. What are the branched chain AA’s? |
|
Definition
|
|
Term
| 504. What can these AA’s generate via transamination rxn? |
|
Definition
| 504. Alphaketovalerate, alpha keto beta methylvalerate, alphaketoisocaproate |
|
|
Term
| 505. What are branched chain AA’s ultimately converted to? |
|
Definition
| 505. propionylCoa or Acetyl CoA |
|
|
Term
| 506. What is homocistunria type 1 caused by? |
|
Definition
| 506. cystathionine synthase deficiency (high homocystine and methionine levels) |
|
|
Term
| 507. What is homocystinuria type 2/3 caused by? |
|
Definition
| 507. deficiency in methl-b-12 and methyl THF synthesis (high serum homocysteine and low methionine levels) |
|
|
Term
| 508. What are some major effects of histamine? |
|
Definition
| 508. major mediator of allergic response via mast cells, constricts lungs in bronchospasms, releases HCl in stomach, excitatory neurotransmitter in brain |
|
|
Term
| 509. What does glycine contain both carbon and N2 for synthesis? |
|
Definition
| 509. Heme, Creatinine, purine bases |
|
|
Term
| 510. What is used to make creatinine? |
|
Definition
| 510. Glycine (kidney) arginine (liver) |
|
|
Term
| 511. What converts guanidoacetate to creatinine? |
|
Definition
|
|
Term
| 512. What is used to measure heart malfunction? Kidney malfunction? |
|
Definition
|
|
Term
| 513. What is the main function of creatinine phosphate? |
|
Definition
| 513. Store phosphate bonds as energy reserve |
|
|
Term
| 514. What isozyme of creatinine is in muscle? Heart? Brain? |
|
Definition
|
|
Term
| 515. What is heme synthesized from? |
|
Definition
|
|
Term
| 516. What are poryphins synthesized from? |
|
Definition
| 516. Gly and Succinyl CoA |
|
|
Term
| 517. What is converted by decarboxylation of Glu? |
|
Definition
|
|
Term
| 518. What is nitric oxide formed from? |
|
Definition
| 518. Arginine using nitric oxide synthase (NOS) (requires NADPH and oxygen) |
|
|
Term
| 519. What are some functions of NO? |
|
Definition
| 519. Vasodilation, neurotransmitter, helps in respiratory burst of macrophages, inhibits platelet aggregation |
|
|
Term
| 520. What are three things Tyr is a precursor to? |
|
Definition
| 520. Pigments-melanin, T4 and T3 hormones, catecholamines |
|
|
Term
| 521. What causes albinism? |
|
Definition
| 521. Deficiency of tyrosinase, (defect in melanin synthesis pathway) |
|
|
Term
| 522. What is tyrosinase related alibinism called? |
|
Definition
| 522. Type 1 oculocutaneous albinism (on chromosome 11) |
|
|
Term
| 523. What is a type of oculocutaneous albinism found on chromosome 15? |
|
Definition
|
|
Term
| 524. Is type 2 as severe as 1? |
|
Definition
|
|
Term
| 525. Is type 3 as severe as 2? |
|
Definition
| 525. No, can’t notice unless from a dark skinned family |
|
|
Term
| 526. What chromosome is ocular albinism associated with? |
|
Definition
| 526. X, effects mostly eye movements |
|
|
Term
| 527. What does iodination of Tyr in thyroglobulin lead to? |
|
Definition
|
|
Term
| 528. How is Tyr converted to Norepi? |
|
Definition
| 528. TyràL DopaàDopaàNorepi |
|
|
Term
| 529. What is norepi converted to in presence of SAM? |
|
Definition
|
|
Term
| 530. What does Epi break down to be excreted in urine? |
|
Definition
| 530. Vanillyl mandelic acid |
|
|
Term
| 531. What is high vanillyl mandelic acid indicative of? |
|
Definition
| 531. Tumor of chromaffin cells |
|
|
Term
| 532. What are some functions of catecholamines? |
|
Definition
| 532. Increase BP, HR,RR, muscle strength, etc. |
|
|
Term
| 533. What is involved in synthesis of serotonin and melatonin (AA)? |
|
Definition
|
|
Term
| 534. What is the function of serotonin? |
|
Definition
| 534. Regulate anger, body temp, mood, sleep, vomiting, sexuality, appetite |
|
|
Term
| 535. What is the function of melatonin? |
|
Definition
| 535. Darkness hormone (circadian cycle), released from pineal gland |
|
|
Term
| 536. T or F: Serotonin is a diamine neurotransmitter |
|
Definition
|
|
Term
| 537. What have low levels of serotonin been associated with? |
|
Definition
| 537. OCD, migraine, IBS, tinnitus, fibromyalgia,etc. |
|
|
Term
| 538. How is melatonin synthesized from serotonin? |
|
Definition
| 538. Acetylation via acetylCoA and methylation via SAM |
|
|
Term
| 539. What is the ring in heme called? |
|
Definition
|
|
Term
| 540. What is the precursor to porphyrin? |
|
Definition
|
|
Term
| 541. Do poryphyrinogens have color? |
|
Definition
| 541. No, but poryphins do |
|
|
Term
| 542. What two substrates does heme arrive from? |
|
Definition
| 542. Gly and succinyl CoA |
|
|
Term
| 543. What contains most of the body’s heme? |
|
Definition
|
|
Term
| 544. What type of Heme is in Hb? |
|
Definition
|
|
Term
| 545. What are some examples of hemoproteins? |
|
Definition
| 545. Cytochromes, catalase, peroxidase, tryptophan |
|
|
Term
| 546. Do hemoproteins need to be synthesized constantly? |
|
Definition
| 546. Yes because they have a short half life |
|
|
Term
| 547. How many rings does heme B have? |
|
Definition
| 547. 4 pyrrole rings (tetrapyrrole) |
|
|
Term
| 548. What links the pyrrole rings? |
|
Definition
|
|
Term
| 549. What types of groups do the porphyrin rings have attached to them in Heme B? |
|
Definition
| 549. Propionyl acid, methyl, vinyl groups |
|
|
Term
| 550. T or F: porphyrinogens are reduced porphyrins |
|
Definition
|
|
Term
| 551. Where is heme (for hemoproteins) synthesized? |
|
Definition
| 551. Erythropoietic tissues and liver |
|
|
Term
| 552. 70% of the heme synthesized in the liver is used for what? |
|
Definition
|
|
Term
| 553. What organelle does heme synthesis begin and end in? |
|
Definition
| 553. Mitochondria (succinyl CoA) goes into cytoplasm then back into mitochondria |
|
|
Term
| 554. T or F: heme regulates its own synthesis |
|
Definition
|
|
Term
| 555. What is the first step in heme synthesis |
|
Definition
| 555. D-aminolevulinic acid is formed from glycine and succinyl CoA in mitochondria via ALA synthase and transported into cytosol |
|
|
Term
| 556. What product eventually comes back into the mitochondria? |
|
Definition
| 556. Copropophyrinogen III |
|
|
Term
| 557. How many steps occur in the cytosol? |
|
Definition
|
|
Term
| 558. What is the regulated step in heme synthesis? |
|
Definition
|
|
Term
| 559. What is a cofactor for ALA synthase? |
|
Definition
|
|
Term
| 560. If there is a deficiency in PLP what can ensue? |
|
Definition
|
|
Term
| 561. How is ALA synthase regulated (3 ways) |
|
Definition
| 561. Allosteric feedback by heme, transcriptional regulation by high or low levels of heme, inhibition of transport of pre-ala synthase from cytosol to mitochondria |
|
|
Term
| 562. What is ALA synthase stimulated by? |
|
Definition
| 562. Requirements for p450’s which include barbiturates and steroids |
|
|
Term
| 563. What enzyme causes two d-ALA’s to condense to form pyrrole ring? |
|
Definition
| 563. ALA dehydratase which forms prophobilinogen ring |
|
|
Term
| 564. What metal can inhibit ALA dehydratase? |
|
Definition
|
|
Term
| 565. What could increased ALA in urine be diagnostic for? |
|
Definition
|
|
Term
| 566. What else could be diagnostic? |
|
Definition
| 566. Decreased prophobilinogen (product of ALA dehydratase) |
|
|
Term
| 567. What two enzymes are needed to form heme from prophobilinogen? |
|
Definition
| 567. Uroporyphyrinogen I synthase & cosynthase, & porphyobilinogen deaminase (forms 4 pyrrole rings) |
|
|
Term
| 568. What does absence of cosynthase result in? |
|
Definition
| 568. Formation of porphyrin rings with no functions (uroporphyrinogen I) which accumulate in urine (congenital erythropoietic porphyria) |
|
|
Term
| 569. What is the difference between uroporphyrinogen I and III? |
|
Definition
| 569. Different side groups (propionyl and acetate is reversed) |
|
|
Term
| 570. What decarboxylates side chains of uroporphyriongen? |
|
Definition
| 570. Uroporphyriongen decarboxylase (makes acetate groups into methyl groups) |
|
|
Term
| 571. What happens after modification of side chains? |
|
Definition
| 571. Coproporphyrinogen III moves to mitochondria |
|
|
Term
| 572. In the mitochondria what converts coproporphyrinogen III into protoporphyrinogen IX? |
|
Definition
| 572. Decarboxylation of propionyl groups into vinyl groups |
|
|
Term
| 573. What converts protoporphyrinogen IX into protoporhhyrin IX? |
|
Definition
| 573. Dehydration to form a conjugated system (antibonding orbital overlap & color) |
|
|
Term
| 574. What enzyme adds lead to protoporphyrin IX? |
|
Definition
| 574. Ferrochelatase (makes heme) |
|
|
Term
| 575. What can inhibit ferrochelatase? |
|
Definition
|
|
Term
| 576. T or F: low concentrations of heme increase ALA synthase levels |
|
Definition
|
|
Term
| 577. What are the two types of porphyrias |
|
Definition
| 577. Erythropoietic & hepatic |
|
|
Term
| 578. T or F: porphyrias are all Autosomal dominant |
|
Definition
| 578. F: all except erythropoietic |
|
|
Term
| 579. Would complete deficiency of a heme biosynthetic enzyme ever happen? |
|
Definition
| 579. No, it would result in death |
|
|
Term
| 580. How does a porphyria defect prior to formation of porphyrinogens present? |
|
Definition
| 580. Accumulate ALA and PBG |
|
|
Term
| 581. How does a porphyria defect after formation of prophyrinogens present? |
|
Definition
| 581. Oxidation of porphyrinogens in skin resulting in cutaneous photosensitivity |
|
|
Term
| 582. What is acute intermittent porphyria? |
|
Definition
| 582. Hepatic uroporphyrinogen I synthase deficiency, PBG and ALA accumulate in urineàdark urine, heme synthesis reduced, ALA is upregulated since heme levels are low, neurological symptoms but not photosensitive |
|
|
Term
| 583. Would barbiturates help a AIP patient? |
|
Definition
| 583. No it would stimulate ALA synthase and worsen the problem by making more ALA and PBG |
|
|
Term
| 584. Do we re-use the components of heme? |
|
Definition
|
|
Term
| 585. What happens to heme? |
|
Definition
| 585. Gets excreted and causes the colors in excrements |
|
|
Term
| 586. What enzyme breaks the heme ring open? |
|
Definition
|
|
Term
| 587. What enzyme makes bilirubin from biliverdin? |
|
Definition
| 587. Biliverdin reductase |
|
|
Term
| 588. Where does most of heme breakdown occur? |
|
Definition
|
|
Term
| 589. What makes bilirubin more soluble for excretion? |
|
Definition
|
|
Term
| 590. What could be some causes of hyperbilirubinemia? |
|
Definition
| 590. High RBC turnover, blockage of bile channels, physiological jaundice of newborn, etc. |
|
|
Term
| 591. Where does ¾ of heme come from? |
|
Definition
|
|
Term
| 592. Where are erythrocytes processed? |
|
Definition
| 592. Spleen, liver, blood marrow |
|
|
Term
| 593. What is the heme ring first cleaved to? |
|
Definition
| 593. Biliverdin by heme oxygenase (biliverdin is a linear tetrapyrrole) |
|
|
Term
| 594. What converts biilverdin to bilirubin? |
|
Definition
| 594. Biliverdin reductase in macrophages |
|
|
Term
| 595. What is bilirubin carried to the liver on? |
|
Definition
|
|
Term
| 596. T or F: bilirubin is an anion |
|
Definition
|
|
Term
| 597. Where is bilirubin conjugated with glucuronic acid? |
|
Definition
|
|
Term
| 598. How many glucuronic acids are conjugated to bilirubin? |
|
Definition
|
|
Term
| 599. What adds glucuronic acid to bilirubin? |
|
Definition
| 599. UDP glucuronic acid via UDP glucuronyl transferase |
|
|
Term
| 600. What is the overall reaction of conjugating BR? |
|
Definition
| 600. UDP glucose+2NAD+àUDP glucuronic acid+2 NADH +2H+ |
|
|
Term
| 601. What is the purpose of conjugation? |
|
Definition
| 601. Make BR more soluble for secretion into bile ducts |
|
|
Term
| 602. What is the rate limiting step of heme breakdown? |
|
Definition
| 602. Conjugated BR being excreted into bile canaliculi (against concentration gradient) |
|
|
Term
| 603. What takes sugars off BR in the intestine? |
|
Definition
| 603. Bacterial enzymes which allow for some reabsorption in the gut |
|
|
Term
| 604. What is the darkening of feces when exposed to air due to? |
|
Definition
| 604. Oxidation of urobilinogens to stercobilinogens |
|
|
Term
| 605. What causes post hepatic jaundice? |
|
Definition
| 605. Gallstones, drugs, inflammation, cancer, etc. |
|
|
Term
| 606. What causes intrahepatic jaundice? |
|
Definition
| 606. Genetic disorders, hepatitis, newborn jaundice, chemical/drugs, Tylenol |
|
|
Term
| 607. What causes prehepatic jaundice? |
|
Definition
| 607. Hemolysis, abnormal Hb, autoimmune disease, etc. |
|
|
Term
| 608. What color is conjugated BR? Unconjugated? |
|
Definition
|
|
Term
| 609. What type of BR can cause neurological problems (kernicterus)? |
|
Definition
|
|
Term
| 610. High BR and high conjugated BR would be diagnostic of ? |
|
Definition
| 610. Post hepatic jaundice (also dx. by high conjugated BR in urine and no urobilinogen) |
|
|
Term
| 611. What is found in the urine in post hepatic jaundice? |
|
Definition
| 611. Conjugated BR, not urobilinogen since it is bypassing intestines from liver and only comes from blood stream |
|
|
Term
| 612. What are some genetic defects that can cause post hepatic jaundice? |
|
Definition
| 612. Dubin Johnson syndrome, rotor’s syndrome (disorders which can conjugate bilirubin but can’t secrete it into bile) |
|
|
Term
| 613. Describe physiological jaundice of the newborn |
|
Definition
| 613. Jaundice after 2 days of birth, very common, no urinary bilirubin or uorbilinogen (no gut bacteria), bilirubin in meconium, treat by using light which isomerizes bilirubin to a less toxic form |
|
|
Term
| 614. What is kernicterus in newborns? |
|
Definition
| 614. Serum bilirubin greater than 15-20mg/dl àunconjugated BR deposited in basal ganglia and causes brain damage (loss of moro reflex, lethargy, encephalopathy can result), treatment is phototherapy or exchange transfusion |
|
|
Term
| 615. What is jaundice with unconjugated hyperbilirubinemia caused by? |
|
Definition
| 615. Deficiency in UDP-GA transferase (gilberts syndrome), crigler najjar syndrome, hepatitis, etc. |
|
|
Term
| 616. Does a mechanism exist to get rid of iron? |
|
Definition
| 616. No (not other than sloughing off cells) |
|
|
Term
| 617. Where do we store iron? |
|
Definition
| 617. Liver and intestinal cells |
|
|
Term
| 618. Where is most iron present at in vivo? |
|
Definition
|
|
Term
| 619. How is the body’s iron content regulated? |
|
Definition
|
|
Term
| 620. What is iron bound to in the liver or intestinal cells? |
|
Definition
| 620. Hemosiderin or ferritin |
|
|
Term
| 621. What transports iron in the serum? |
|
Definition
|
|
Term
| 622. In blood what oxidation state of iron can cross plasma membrane? What oxidation form is iron stored as? |
|
Definition
|
|
Term
| 623. If iron is not needed how is it disposed of? |
|
Definition
| 623. Rapid sloughing off of intestinal cells |
|
|
Term
| 624. What is most of the fuel stored as in the body? |
|
Definition
|
|
Term
| 625. Does glycogen metabolism in muscle respond to signals from insulin/glucagon? |
|
Definition
|
|
Term
| 626. What does excess breakdown of protein result in ? |
|
Definition
|
|
Term
| 627. What does skeletal muscle export in the resting state? |
|
Definition
|
|
Term
| 628. What does skeletal muscle export in prolonged exercise? |
|
Definition
|
|
Term
| 629. What are the substrates for gluconeogenesis? |
|
Definition
| 629. Lactate, alanine, glycerol |
|
|
Term
| 630. What are the substrates for Glycogenesis? |
|
Definition
| 630. Glc 1 phosphate, Glc |
|
|
Term
| 631. How many days after starvation do ketone body levels significantly rise? |
|
Definition
|
|
Term
| 632. What cycle transports lactate and glucose between RBC’s and the liver? |
|
Definition
|
|
Term
| 633. What are the two key fuels in the fasting state? |
|
Definition
| 633. B-hydroxybutyrate, acetoacetate (note dr. nishimoto’s last exam question is contrary to this) |
|
|
Term
| 634. T or F: when a fasting person is refed it takes time for normal fed state to be re-established. |
|
Definition
|
|
Term
| 635. When do ketones become the primary source of fuel for the brain? |
|
Definition
| 635. 20-40 day starvation |
|
|
Term
| 636. What is the major anabolic hormone? |
|
Definition
|
|
Term
| 637. What are some counterregulatory hormones to insulin? |
|
Definition
| 637. Glucagon, epi, norepi, cortisol, somatostatin, GH, TH |
|
|
Term
| 638. What stimulates release of insulin? |
|
Definition
|
|
Term
| 639. What inhibits release of insulin? |
|
Definition
|
|
Term
| 640. T or F: glucagon increases ketogenesis |
|
Definition
|
|
Term
| 641. What mobilizes fuels during acute stress? |
|
Definition
|
|
Term
| 642. What provides for changing requirements over long term (hormone)? |
|
Definition
|
|
Term
| 643. What are mechanisms regulating liver metabolism? |
|
Definition
| 643. Substrate supply, allosteric effects, phosphorylation, adaptive enzymes |
|
|
Term
| 644. G6P DH is in what organelle? |
|
Definition
|
|
Term
| 645. 20 yr old boy is starving for 30 hours, what is main source of primary fuel for brain? |
|
Definition
|
|
Term
| 646. A sailor has been fasted for 7 days, the suddenly jumps overboard to swim to shore, where does his fuel come from? |
|
Definition
| 646. Muscle glycogen, (used during periods of exertion or maximal activity, if it was a slow relaxed swim it might have been fatty acids or ketones) |
|
|
